547736 Tailoring a Metabolic Model for CHO Cell-Line By Integrating Data-Inferred Metabolic Activities

Sunday, October 14, 2018
Song-Min Schinn1, Wei Wei2, Yifeng Xu2, Carly Morrison2, Lin Zhang2 and Nathan Lewis3, (1)University of California, San Diego, La Jolla, CA, (2)Pfizer, Andover, MA, (3)Department of Bioengineering, University of California, San Diego, CA

CHO cells are widely used in commercial production of biotherapeutics. Despite this, CHO bioprocesses have traditionally been developed empirically, due to a limited understanding of their biology. Now, an increased knowledge of CHO cell biology can be exploited to improve production and control. A promising platform for such rational engineering is genome-scale metabolic network models, which describe metabolism mathematically. These models can predict cell-line specific metabolic features when integrated with omics data, based on key assumptions on gene expression regulation and gene-to-reaction relationships. Here, we deployed a novel approach that uses transcriptomic data to define a cells' metabolic functions, and then used these to build a metabolic model for a CHO-K1-derived industrial producer cell-line. We have used the resulting model to predict key reaction fluxes for multiple bioprocess settings, and it can be applied for rational bioprocess optimization.

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